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N. Di Girolamo, D. Wakefield, M.T. Coroneo; UVB–Mediated Induction of Cytokines and Growth Factors Through Cell–Surface Receptors and Intracellular Signaling Pathways in Pterygium Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4981.
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© ARVO (1962-2015); The Authors (2016-present)
Pterygium is an invasive ocular surface disease associated with excessive ultraviolet (UV) exposure. The aims of this investigation were to identify UV activated signaling pathways in pterygium epithelial cells (PEC) that mediate cytokine and growth factor production and to determine whether these pathways could be blocked by anti–inflammatory agents such as retinoic acid (RA) and interferon–alpha (IFN–α).
PEC were pre–treated with or without inhibitors of the ERK1/2, JNK, and p38 (PD98059, SB202190, SB203580) mitogen activated protein kinases (MAPK) or with inhibitors of the tyrosine kinase activity of epidermal growth factor receptor (EGFR; PD153035) and platelet derived growth factor (PDGF; AG1295). Cell were then exposed to UVB (20 mJ/cm2) and further treated with the same inhibitors. Conditioned media was harvested and analyzed for interleukin (IL)–6, and IL–8 and vascular endothelial growth factor (VEGF) by ELISA. Cytokine mRNA was assessed by reverse transcription polymerase chain reaction (RT–PCR).
MAPK inhibitors significantly abolished the UVB–mediated increase in IL–6, IL–8, and VEGF. The EGFR inhibitor reduced IL–8, while the PDGFR inhibitor suppressed IL–6, and both inhibitors partially down–regulated VEGF production in UV exposed PEC. RA and IFN–α dose–dependently abrogated IL–6 and IL–8 but had little effect on VEGF.
Our results have identified a stress induced intracellular pathway and potential cell–surface transmitters that may be relevant to pterygium development. Moreover, we have identified two anti–inflammatory/anti–angiogenic agents that reduced cytokine production in our culture model and may be a therapeutic option worth considering for patients with pterygia.
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